Heterogeneity in diagnostic criteria for chronic kidney disease of undetermined etiology (CKDu): a systematic review of the literature

Background: Chronic kidney disease (CKD) of undetermined etiology (CKDu) is an important public health problem. It is a diagnosis of exclusion and the diagnostic approach varies widely across geographies. We aimed to systematically examine criteria used to diagnose CKDu in published literature.

Method: PubMed, Medline, Embase, and Web of Science were searched systematically for published studies and conference abstracts pertaining to CKDu using relevant search terms. Systematic reviews/meta-analyses and reviews were screened to identify additional studies. Findings are presented in tables and figures and discussed critically.

Results: 60 studies were identified which mention the definition used to diagnose CKDu. A combination of pre-specified estimated glomerular filtration rate (eGFR) and proteinuria/albuminuria cut-offs was used as diagnostic criteria in only 18 studies (30%), while another 11 studies (18.3%) relied solely on proteinuria/albuminuria cut-offs.Nineteen studies classified all CKD patients without any identifiable cause as CKDu irrespective of level of proteinuria/albuminuria. 18 studies excluded patients with significant proteinuria/albuminuria, although cut-offs used for exclusion varied. Limited studies mention the criteria used to exclude diabetes(n = 22) and hypertension(n = 23) related kidney disease, the two most common causes of CKD with wide variability.

Conclusions: There is considerable variability in diagnostic criteria used to define CKDu in epidemiologic studies, especially in excluding proteinuria and other causes of kidney disease. Such heterogeneity may cause misclassification and erroneous estimation of disease burden making comparisons between studies difficult.

Clinical trial number: Not applicable.